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Schumann, Gunter;
Liu, Chunyu;
O’Reilly, Paul;
Gao, He;
Song, Parkyong;
Xu, Bing;
Ruggeri, Barbara;
Amin, Najaf;
Jia, Tianye;
Preis, Sarah;
Lepe, Marcelo Segura;
Akira, Shizuo;
Barbieri, Caterina;
Baumeister, Sebastian;
Cauchi, Stephane;
Clarke, Toni-Kim;
Enroth, Stefan;
Fische, Kristar;
Hällfors, Jenni;
Harris, Sarah E.;
Hieber, Saskia;
Hofer, Edith;
Hottenga, Jouke-Jan;
Johansson, Åsa;
[...]
KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference
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- Medientyp: E-Artikel
- Titel: KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference
- Beteiligte: Schumann, Gunter; Liu, Chunyu; O’Reilly, Paul; Gao, He; Song, Parkyong; Xu, Bing; Ruggeri, Barbara; Amin, Najaf; Jia, Tianye; Preis, Sarah; Lepe, Marcelo Segura; Akira, Shizuo; Barbieri, Caterina; Baumeister, Sebastian; Cauchi, Stephane; Clarke, Toni-Kim; Enroth, Stefan; Fische, Kristar; Hällfors, Jenni; Harris, Sarah E.; Hieber, Saskia; Hofer, Edith; Hottenga, Jouke-Jan; Johansson, Åsa; [...]
- Erschienen: National Academy of Sciences, 2016
- Erschienen in: Proceedings of the National Academy of Sciences of the United States of America
- Umfang: 14372-14377
- Sprache: Englisch
- ISSN: 0027-8424; 1091-6490
- Zusammenfassung: <p>Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified β-Klotho (<italic>KLB</italic>) as a locus associated with alcohol consumption (rs11940694; <italic>P</italic> = 9.2 × 10<sup>−12</sup>). β-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific β-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver–brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.</p>
- Beschreibung: <p>Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified β-Klotho (<italic>KLB</italic>) as a locus associated with alcohol consumption (rs11940694; <italic>P</italic> = 9.2 × 10<sup>−12</sup>). β-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific β-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver–brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.</p>
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- Zugangsstatus: Freier Zugang